2367. Six-month Humoral Response Following Two Or Three Doses Of Covid-19 Vaccines As Primary Vaccination Followed Or Not By a Booster Dose In Specific Populations – ANRS0001S COV-POPART Cohort Study

Abstract Background The duration of humoral response in immunocompromised populations according to the number of doses in the primary vaccine regimen and the number of booster doses is little known. Methods Participants from the French national multi-center prospective cohort study ANRS0001S COV-POPART were included (11 specific subpopulations and 2 control groups (18-64 years and over 65 years)). We evaluated the immune response to COVID-19 vaccines up to 6 months after the second dose, distinguishing participants having received two or three doses in their initial vaccination scheme and those with or without a booster dose before 6 months. Participants with positive anti-nucleocapsid (NP) antibodies or SARS-CoV-2 infection during follow-up were excluded. Serological (ELISA EuroImmun®) and seroneutralisation (in vitro neutralization assay, original strain) tests were carried out centrally. Results 3724 participants were included: 2756 from specific subpopulations and 968 controls. Participants in specific sub-populations and the control groups mostly received two doses of BNT162b2 (68.6% and 83.6%, respectively). Fifteen percent of participants in a specific sub-population received 3 doses within their initial vaccine scheme (mostly solid organ transplants (SOT) and Hematopoietic stem cell transplants (HCT)) and 11.2% received a booster dose within 6 months after a median time of 5 months after the last dose. The control groups and all specific sub-populations who received two doses as the primary regimen, except solid SOT and HCT groups, increased their anti-Spike and seroneutralisation titer after a booster dose (Figure 1A and 1C). The booster dose had little effect on participants who received three doses as a primary vaccination regimen compared to those who did not receive the booster dose (Figure 1B and 1D). 6-month median (IQR) anti-Spike IgG titers (BAU/mL) in specific subpopulations who received two (A) and three doses (B) within their initial vaccine scheme. 6-month seroneutralisation titers in specific subpopulations who received two (C) and three doses (D) within their initial vaccine scheme. Solid organ transplantation (SOT), hematopoietic stem cell transplantation (HCT), chronic renal failure (CKD), systemic autoimmune diseases (SAD), inflammatory rheumatic diseases (IRD), multiple sclerosis (MS) or neuromyelitis optica spectrum disorders (NMOSD). Conclusion A booster dose in those who received 2 doses as a primary vaccination regimen increased 6-month humoral responses in almost all sub-populations except SOT and HSCT. The effect of booster doses in those receiving three doses as a primary vaccination regimen was low, reflecting the profound immunosuppression of these patients. Disclosures Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant|Astrazeneca: Board Member|Moderna: Board Member|Pfizer: Advisor/Consultant|Pfizer: Board Member Odile Launay, MD, PhD, Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Board Member

control groups (18-64 years and over 65 years)).We evaluated the immune response to COVID-19 vaccines up to 6 months after the second dose, distinguishing participants having received two or three doses in their initial vaccination scheme and those with or without a booster dose before 6 months.Participants with positive antinucleocapsid (NP) antibodies or SARS-CoV-2 infection during follow-up were excluded.Serological (ELISA EuroImmun®) and seroneutralisation (in vitro neutralization assay, original strain) tests were carried out centrally.
Results.3724 participants were included: 2756 from specific subpopulations and 968 controls.Participants in specific sub-populations and the control groups mostly received two doses of BNT162b2 (68.6% and 83.6%, respectively).Fifteen percent of participants in a specific sub-population received 3 doses within their initial vaccine scheme (mostly solid organ transplants (SOT) and Hematopoietic stem cell transplants (HCT)) and 11.2% received a booster dose within 6 months after a median time of 5 months after the last dose.The control groups and all specific subpopulations who received two doses as the primary regimen, except solid SOT and HCT groups, increased their anti-Spike and seroneutralisation titer after a booster dose (Figure 1A and 1C).
The booster dose had little effect on participants who received three doses as a primary vaccination regimen compared to those who did not receive the booster dose (Figure 1B and 1D).
6-month median (IQR) anti-Spike IgG titers (BAU/mL) in specific subpopulations who received two (A) and three doses (B) within their initial vaccine scheme.6-month seroneutralisation titers in specific subpopulations who received two (C) and three doses (D) within their initial vaccine scheme.
Conclusion.A booster dose in those who received 2 doses as a primary vaccination regimen increased 6-month humoral responses in almost all sub-populations except SOT and HSCT.The effect of booster doses in those receiving three doses as a primary vaccination regimen was low, reflecting the profound immunosuppression of these patients.
Disclosures.Paul LOUBET, MD, PhD, Astrazeneca: Advisor/Consultant| Astrazeneca: Board Member|Moderna: Board Member|Pfizer: Advisor/Consultant| Pfizer: Board Member Odile Launay, MD, PhD, Moderna: Advisor/Consultant| Pfizer: Advisor/Consultant|Pfizer: Board Member 1 National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 2 Children's National Hospital, Washington, District of Columbia 3 Food and Drug Administration, Silver Spring, Maryland 4 Yale School of Medicine, New Haven, Connecticut + RBD + ) in the blood, tonsils, and adenoids of nearly all infected and vaccinated subjects.Tonsils and adenoids post-infection had a higher percentage of S1 + RBD + memory B cells than postvaccination, but differences in the percentage of S1 + RBD + cells were not noted in the peripheral blood.Furthermore, we found that only 20% of vaccinated only subjects had SARS-CoV-2-specific germinal center B cells in their tissues compared to over 70% of infected subjects and subjects with hybrid immunity.Unsupervised analyses of the high dimensional flow cytometry data revealed differences in the characteristics of SARS-CoV-2-specific B cells post-vaccination and post-infection; S1 + RBD + B cells from infected subjects had a higher portion of CXCR3 + and IgA + memory B cells, while those from vaccinated subjects had a greater proportion of CD21 lo memory B cells in the blood and tissues, implying a greater extrafollicular response postvaccination but stronger mucosal IgA and IFN-γ-induced B cell responses post-infection.96.5 (1.7) vs 96.7 (1.9), p=0.555], respectively.After infection, HCWs had significantly increased TAbs levels in all time points compared to non-infected vaccinated HCWs (Table 1).In non-infected HCWs, a negative association of TAbs and NAbs levels with age was detected after the 2 nd and 3 rd vaccine dose (p< 0.05).No association was found in 8 months after the 3 rd dose between antibody levels and demographic and clinical parameters.

1 First
Department of Pediatrics, Infectious Diseases and Chemotherapy Research Laboratory, Medical School, National and Kapodistrian University of Athens, 'Aghia Sophia' Children's Hospital, Athens, Greece, Athens, Attiki, Greece 2 University Research Institute for Maternal and Child Health and Precision Medicine, Athens, Greece, Athens, Attiki, Greece 3 National and Kapodistrian University of Athens, Athens, Attiki, Greece nd and 3 rd doses of the BNT162b2 mRNA COVID-19 vaccine with epidemiological parameters and breakthrough infection is limited.